Inhibition of retinopathy of prematurity in rat by intravitreal injection of sorafenib

Abstract

AIM:To investigate the effect of intravitreal injection administered sorafenib, a multikinase inhibitor, in a rat model of oxygen-induced retinopathy (OIR).METHODS:Seven-day-old Sprague-Dawley rats (n=144) were randomly assigned to six groups. Group A received normal partial oxygen pressure and groups B, C, D, E and F were exposed to hyperoxia (75±2)% from postnatal 7d (P7) to P12 to induce retinopathy of prematurity. The rats in groups C, D, E and F were received intravitreal injections of either vehicle (DMSO) or sorafenib at P12 (5, 20 and 80 μg, respectively). Then they returned to normoxia after P12. The retinas were whole-mounted and imaged with a confocal microscopy. The vascular branching points were counted to quantify neovascularization at P17. Cross-sections of the retina were stained with hematoxylin and eosin (HE). The nuclei of new vessels breaking the internal limiting membrane were counted to quantify the proliferative neovascular response.RESULTS:The retinal vessel in groups B and C turned into tortuosity and a great deal of neovascularization were observed. Sorafenib-treated rats had significantly less neovascularization as compared with vehicle-treated and control rats in a dose dependent manner (P<0.05). The number of vascular branching points in A, B, C, D, E and F were 16.50±3.90, 37.44±6.47, 37.08±5.10, 30.80±6.85, 26.08±5.08 and 19.83±3.51, respectively. The number of the nuclei of retinal new vessel in A, B, C, D, E and F were 0.22±0.42, 35.66±4.70, 35.30±4.54, 27.30±4.28, 21.41±3.53, and 7.41±2.87, respectively. There were significant difference between each group (P＜0.05) except groups B and C.CONCLUSION: In the rat OIR model, sorafenib could inhibit retinal neovascularization in a dose dependent manner.

Keywords

• sorafenib
• retinopathy of prematurity
• neovascularization
• tyrosine kinase inhibitors
• tyrosine kinase inhibitors